Schematic of intestinal iron uptake. Fe3+ in the intestinal lumen is converted into Fe2+ by DcytB, and Fe2+ is then transported across the apical membrane of enterocytes by the transmembrane transporter DMT1. Dietary heme can also be transported across the apical membrane by a yet unknown mechanism. HCP1 is a putative heme transporter that transports heme across the apical membrane of enterocytes into the cytosol. Heme is subsequently metabolized in the cytosol by HO-1 (localized at endoplasmic reticulum membrane facing cytosol) to liberate Fe2+. Iron is then stored in ferritin or eventually exported across the basolateral membrane into the bloodstream via Fe2+ transporter FPN1. The FPN1-mediated efflux of Fe2+ is coupled by its re-oxidation to Fe3+, catalysis by the membrane-bound ferroxidase HP, and possibly also by its plasma homologue Cp.